Several skin diseases may present as vesicles or bullae. Immunofluorescent studies are very helpful in differentiating the various disease entities. Familiarity with the procedure and the various kinds of patterns that are specific and non-specific is essential for the practicing dermatologist. Immunofluorescent patterns are particularly helpful in differentiating pemphigus, bullous pemphigoid, cicatrical pemphigoid, herpes gestationis, dermatitis herpetiformis, linear IgA dermatosis and porphyria. Immunofluorescent studies of the skin and sera of these patients were vital to an understanding their pathogenesis. Immunoelectron microscopy has further helped in delineating the exact sites of immunoglobulin deposition, and, thus, identifying the location of the antigens. In pemphigus, studies at the molecular level reveal that the basic pathological process is mediated by an anti-cellular cement substance antibody. The binding of this antibody at the cell surface level results in a process that is seen at the light microscopy level in the form of acantholysis. In bullous pemphigoid cells may play an important role. It appears that the mast cell, eosinophil, and the lymphocyte in harmony with the polymorphonuclear leucocyte work together to bring about an enzymatic degradation of the basement membrane. The specific role of the anti-basement membrane zone antibody is also under current study. With advances in molecular immunology, especially monoclonal antibodies and gene technology, it is hoped that these cellular and molecular interactions will be better understood and further defined.